Heparin is a polysaccharide present in a variety of organs and tissues, particularly liver, lung, and the large arteries. It is a polymer of repeating units of D-glucuronic acid usually having an O-sulfate group at C-2 and D-glucosamine N-sulfate with an additional O-sulfate group at C-6. Both the linkages of the polymer are alternating -1,4, and it is thought that seven of the eight glucuronic acid residues in the polymer exhibit an O-sulfate group. The postulated repeating unit is shown as follows; ##STR1## as defined by Jaques, Science, 206, 529 (1979) and Rawn, Biochemistry, 297-298 (1983). Heparin is commonly provided as the sodium salt, sometimes referred to as sodium heparinate or heparin sodium, as indicated in U.S. Pat. No. 3,062,716 (Montaudraud) and as "Entry 4543" in The Merck Index, 672 (10th edn. 1983).
One of the major properties of heparin which has been recognized for some time is its ability to prolong the clotting time of blood both in vivo and in vitro. Less well known properties of heparin are that it stimulates healing of burn wounds and its ability to reverse ischemic myocardial injuries. For instance, Saliba et al. in J. Amer. Med. Assoc., 225, 261 (1973) describe the application of heparin-administered parenterally and topically to humans suffering from second and third degree burns. Heparin both relieves the pain and prevents the initial burn size from expanding. Most important, there is enhanced revascularization, granulation and re-epithelialization. The effect of heparin on burn wound healing is critically dose-related, dose-dependent and pH regulated (Saliba, Thrombosis and Haemostasis, 40, No. 1 (1978)). Most applications of heparin as a therapeutic agent have used concentrations in the range of 20,000 to 40,000 units/per milliliter for intravenous or subcutaneous modes of presentation, while for topical applications concentrations in the range of 5,000 to 10,000 units/per milliliter have been employed. The beneficial effect of heparin on reversing myocardial ischemic injury generally has been shown to require the administration of 10,000 to 100,000 units total of 5,000 to 10,000 units/ml heparin, with favorable results being apparent acutely on electrocardiograms and on cardiac enzymes monitored at 24 and 48 hours.
In addition to the above effects of heparin, the molecule is also thought to exhibit antithrombin, antiplatelet-lysis, thrombolytic, antihistaminic, antiserotonin and antiproteolytic enzymatic activity. The mechanism whereby heparin exerts all these effects is not known. Lastly, heparin has also been shown to be effective in treating weeping poison oak dermatitis (Saliba and Griner Aerospace Medicine, 41, 2, 179 (1970)) and weeping ear eczema and acute tracheal bronchitis (Dougherty and Dolowitz, Amer. J. Cardiol. 14, 18 (1964)).
The following U.S. patents show various medical applications for heparin or related compounds. U.S. Pat. No. 3,062,716 shows a method of treating hemorrhoids. U.S. Pat. No. 3,137,624 describes compositions for treating defective veins wherein one component is heparin. U.S. Pat. No. 3,244,594 describes heparin compounds having antitumor activity. U.S. Pat. No. 3,151,025 describes a composition that rids the blood of lipoprotein molecules. U.S. Pat. No. 4,039,665 shows a method of composition containing heparin for eradication of venous blemishes. Lastly, U.S. Pat. No. 4,390,532 shows another composition with heparin that is useful for topical applications in treating wrinkles, acne and androgen baldness.